Systems and Methods for Improving Heart Rate Kinetics in Heart Failure Patients

ABSTRACT

Adaptive rate pacing for improving heart rate kinetics in heart failure patients involves determining onset and sustaining of patient activity. The patient&#39;s heart rate response to the sustained activity is evaluated during a time window defined between onset of the activity and a steady-state exercise level. If the patient&#39;s heart rate response to the sustained activity is determined to be slow, a pacing therapy is delivered at a rate greater than the patient&#39;s intrinsic heart rate based on a profile of the patient&#39;s heart rate response to varying workloads. If determined not to be slow, the pacing therapy is withheld. Monitoring-only configurations provide for acquisition and organization of physiological data for heart failure patients. These data can be acquired on a per-patient basis and used to assess the HF status of the patient.

RELATED APPLICATIONS

This application is a division of U.S. patent application Ser. No.11/478,015 filed on Jun. 29, 2006, to which Applicant claims priorityunder 35 U.S.C. § 120, and which is incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates generally to monitoring and treating heartfailure patients that suffer from delayed oxygen kinetics during theonset to activities.

BACKGROUND OF THE INVENTION

It is known that the heart's natural pacemaker (i.e., the sinus node)for many cardiac patients, particularly heart failure patients, providesan adequate heart rate for producing a cardiac output satisfactory forlow levels of exertion, but not for high levels of exertion. This isknown as chronotropic incompetence. Adaptive rate pacing has, in thepast, been applied to patients to improve the chronotropic response toactivities.

Rate responsive pacemakers have been developed that incorporate multiplesensors for measuring physiologic demand and for developing a controlsignal for delivering adaptive rate pacing under appropriatecircumstances. For example, rate responsive pacemakers may incorporatean accelerometer for detecting patient movement and a minute ventilationsensor for detecting respiratory activity as an indicator of physiologicdemand. When a patient having such a pacemaker implanted goes from aresting state to a minimal level of activity, the accelerometer willrespond to the patient's stepping rate and the minute ventilation sensorwill respond to the increased metabolic demand resulting in an increasedpaced heart rate from one or both of the sensors.

The physiologic sensors of rate responsive pacemakers provide inputs toa microprocessor-based controller for adjusting the rate at whichcardiac pacing pulses are delivered to meet physiologic demand. It isdifficult to predict an appropriate pacing function capable ofgenerating a paced rate corresponding to a patient's metabolic demand atthe time of implanting the pacemaker in the patient. Notwithstanding theefficacy of conventional rate responsive pacemakers, adjustments to thepacing rate by the microprocessor-based controller are made using aresponse factor that is based on estimated activity levels and targetheart rates. Inappropriately computing or adjusting the response factormay result in a paced rate that is too high or too low for a givenmetabolic demand. If the paced rate is too high, the patient may feelpalpitated or stressed. If too low, the patient may feel fatigued, tiredor dizzy.

SUMMARY OF THE INVENTION

The present invention is directed to systems and methods for adaptivelypacing a heart failure patient in response to the onset of patientactivity. Adaptive pacing according to embodiments of the presentinvention is implemented to improve the mean heart rate response to theonset of exercise or activity of heart failure patients, resulting inimproved oxygen kinetics and reducing the dependency on anaerobicmetabolism.

The present invention is also directed to systems and methods forcollecting, organizing, and analyzing data collected from heart failurepatients. These data can be acquired on a per-patient basis and used toassess the HF status of the patient and to develop a physiologic profilefor the patient. These data can also be used during adaptive rate pacingto improve heart rate kinetics in heart failure patients in the contextof embodiments that provide for cardiac pacing therapies.

In accordance with embodiments of the present invention, methods foradaptively pacing a heart failure patient involve determining onset ofpatient activity and sustaining of the patient activity. Such methodsfurther involve determining, for a time window defined between onset ofthe activity and a steady-state exercise level, whether the patient'sheart rate response to the sustained activity is slow relative to anactivity level of the patient. If the patient's heart rate response tothe sustained activity is determined to be slow, a pacing therapy isdelivered at a rate greater than the patient's intrinsic heart ratebased on a profile of the patient's heart rate response to varyingworkloads. If the patient's heart rate response to the sustainedactivity is determined not to be slow, the pacing therapy is withheld.

Determining whether or not the patient is engaged in a sustainedactivity may involve sensing that the patient has been active for a timeduration exceeding a threshold ranging between about 30 seconds andabout 6 minutes. Determining whether or not the patient is engaged in asustained activity may involve determining that the patient's strokevolume has reached a steady-state value in response to the patientactivity.

The pacing therapy is delivered at a rate sufficient to increase thepatient's heart rate response for reaching the steady-state exerciselevel of the sustained activity. In general, the pacing therapy isdelivered at a rate sufficient to improve a chronotropic response of thepatient to the sustained activity. Delivering the pacing therapytypically comprises adjusting an AV delay and/or VV delay parameter ofthe pacing therapy. An upper rate limit of the pacing therapy may beadjusted based on the patient's profile.

The patient profile may include one or both of the patient's intrinsicheart rate and minute ventilation at varying activity levels. Thepatient profile may include the patient's mean heart rate response timeat varying activity levels. The patient's profile may be developed usingan implantable medical device during a learning procedure. The learningprocedure may involve acquiring one or more of heart rate, minuteventilation, and mean heart rate response time for the patient atvarying activity levels. In one embodiment, the patient profilecomprises a heart rate and a minute ventilation associated with each ofa number of activity level ranges, and slowness of the patient's heartrate response is determined based on heart rate and minute ventilationvalues established for an activity level range of the profilecorresponding to the patient's actual activity level.

In accordance with other embodiments of the present invention, animplantable cardiac device may include a number of electrodespositionable relative to a patient's heart, an activity sensorconfigured to detect activity of the patient, and a physiologic sensorconfigured to measure physiologic demand of the patient. A memory may beconfigured to store patient profile data. The patient profile datapreferably includes heart rate and heart rate response data relative tovarying workloads established for the patient.

A processor is coupled to the electrodes, activity sensor, physiologicsensor, and memory. The processor is configured to determine onset ofpatient activity and sustaining of the patient activity as measured bythe activity sensor. The processor is further configured to determinewhether the patient's heart rate response to the sustained activity asmeasured by the physiologic sensor is slow relative to an activity levelof the patient during a time window defined between onset of theactivity and a steady-state exercise level. The processor is alsoconfigured to deliver a pacing therapy at a rate greater than thepatient's intrinsic heart rate based on the patient profile data if thepatient's heart rate response to the sustained activity is determined tobe slow. The processor is preferably configured to withhold the pacingtherapy in response to the processor determining that the patient'sheart rate response to the sustained activity is not slow.

The processor may be configured to determine sustaining of the patientactivity in response to sensing an output signal produced by theactivity sensor indicative of sustained patient activity for a timeduration exceeding a threshold ranging between about 30 seconds andabout 6 minutes. The processor may be configured to determine sustainingof the patient activity in response the patient's stroke volume reachinga steady-state value in response to the activity. The processor may beconfigured to determine sustaining of the patient activity in responseto sensing an output signal produced by the activity sensor and thephysiologic sensor, respectively.

The activity sensor may include an accelerometer or other rate sensor.The physiologic sensor may include a minute ventilation sensor or apressure sensor.

The processor may be configured to adjust an upper rate limit of thepacing therapy based on the patient's profile. The processor may beconfigured to adjust an AV delay and/or VV delay parameter of the pacingtherapy.

The processor may be configured to acquire patient profile datacomprising one or both of the patient's intrinsic heart rate and minuteventilation. The processor may be configured to acquire patient profiledata comprising mean heart rate response time data at varying activitylevels. The patient profile data is preferably stored in the memory ofthe device. The processor may determine slowness of the patient's heartrate response based on patient profile data associated with an activitylevel of the profile corresponding to the patient's actual activitylevel.

The above summary of the present invention is not intended to describeeach embodiment or every implementation of the present invention.Advantages and attainments, together with a more complete understandingof the invention, will become apparent and appreciated by referring tothe following detailed description and claims taken in conjunction withthe accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a flow diagram of a method for reducing a patient's mean heartrate response to the onset of activity in accordance with embodiments ofthe present invention;

FIG. 2 is a flow diagram of a method for reducing a patient's mean heartrate response to the onset of activity in accordance with otherembodiments of the present invention;

FIG. 3 is a graph showing various aspects of an adaptive rate pacingtherapy that improves a patient's mean heart rate response to the onsetof activity implemented in accordance with the principles of the presentinvention;

FIG. 4 is a flow diagram of a method for developing a patient profileuseful for assessing the status of a heart failure patient in accordancewith embodiments of the present invention, and for implementing anadaptive rate pacing therapy for reducing a patient's mean heart rateresponse to the onset of activity in accordance with other embodimentsof the present invention;

FIG. 5 is a block diagram of a device configured for developing apatient profile useful for assessing the status of a heart failurepatient in accordance with embodiments of the present invention, and forimplementing an adaptive rate pacing therapy for reducing a patient'smean heart rate response to the onset of activity in accordance withother embodiments of the present invention;

FIG. 6 is an illustration of an implantable cardiac device including alead assembly shown implanted in a sectional view of a heart, theimplantable cardiac device configured to implement methodologies of thepresent invention; and

FIG. 7 is an illustration of an implantable medical device including asubcutaneous, non-intrathoracic lead assembly shown implanted outsidethe ribcage, the implantable medical device configured to implementmethodologies of the present invention.

While the invention is amenable to various modifications and alternativeforms, specifics thereof have been shown by way of example in thedrawings and will be described in detail below. It is to be understood,however, that the intention is not to limit the invention to theparticular embodiments described. On the contrary, the invention isintended to cover all modifications, equivalents, and alternativesfalling within the scope of the invention as defined by the appendedclaims.

DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS

In the following description of the illustrated embodiments, referencesare made to the accompanying drawings, which form a part hereof, and inwhich is shown by way of illustration, various embodiments in which theinvention may be practiced. It is to be understood that otherembodiments may be utilized, and structural and functional changes maybe made without departing from the scope of the present invention.

A medical device according to the present invention may include one ormore of the features, structures, methods, or combinations thereofdescribed hereinbelow. For example, a cardiac monitor, cardiacstimulator, or other type of implantable or patient-external medicaldevice may be implemented to include one or more of the advantageousfeatures and/or processes described below. It is intended that such amonitor, stimulator, or other external, implanted or partially implanteddevice need not include all of the features described herein, but may beimplemented to include selected features that provide for usefulstructures and/or functionality. Such a device may be implemented toprovide a variety of therapeutic or diagnostic functions.

A wide variety of implantable medical devices, such as cardiacmonitoring and/or stimulation devices, may be configured to implement anadaptive rate pacing methodology and a patient profiling methodology ofthe present invention. A non-limiting, representative list of suchdevices includes cardiac monitors, pacemakers, cardiovertors,defibrillators, resynchronizers, and other cardiac sensing and therapydelivery devices. Such devices are referred to herein generally as apatient-implantable medical device (PIMD) for convenience.

The present invention is directed to systems and methods for improvingheart rate kinetics in heart failure (HF) patients. Embodiments of thepresent invention are directed to reducing the time of the heart ratekinetics to steady-state activity. Embodiments of the present inventionare also directed to improving the chronotropic response of a heartfailure patient to activity and reducing their dependency on anaerobicmetabolism.

The present invention is also directed to systems and methods forcollecting, organizing, and analyzing data collected from heart failurepatients. These data can be acquired on a per-patient basis and used toassess the HF status of the patient. These data can also be used duringadaptive rate pacing to improve heart rate kinetics in heart failurepatients.

During the onset to activities, heart failure patients demonstrate adelay in oxygen and heart rate kinetics, resulting in a higherdependency on anaerobic metabolism and a higher possibility of earlytermination of activities, such a exercise. One of the primary reasonsfor the delay to steady-state oxygen consumption is a reduced mean heartrate response to the onset of exercise. Reduced oxygen kinetics in heartfailure patients is exemplified by a slower than normal heart rateresponse during the kinetic phase. A delayed rise in peak oxygenconsumption in response to exercise may be responsible for subnormalvalues of peak oxygen consumption early in exercise in heart failurepatients.

The mean response time of the heart rate kinetics to steady state can bedetermined via a time constant. For example, the heart rate meanresponse time may determined as follows:

${H\; R_{M\; R\; T}} = \frac{{H\; R_{S\; S}} - {H\; R_{S\; E}}}{C\; H\; R}$

where HR_(MRT) is the heart rate mean response time, HR_(SS) is theheart rate at steady state exercise, HR_(SE) is the heart rate deficitat the start of exercise, and CHR is the change in heart rate.

The delayed time to steady-state exercise determined during the earlyphase of exercise reflects a delayed cardiac output response in patientswith severely impaired left ventricular function. The time tosteady-state exercise is a sensitive and discriminate measure ofimpaired cardiac reserve. Data acquired during the kinetic phase may beused to assess the HF status of a given patient, and subsequently usedas a basis for making adjustments to an adaptive rate pacing therapydelivered to the patient during the kinetic phase.

According to embodiments of the present invention, devices and methodsof the present invention are directed to improving oxygen kinetics inheart failure patients by reducing the time to steady-state based onmeasuring the intrinsic heart rate to steady-state of an activity. Oncethe start of an activity has been declared and the activity has beensustained for a meaningful period of time, the patient's intrinsic heartrate response is measured in terms of time to steady-state during theperiod of activity. If the heart rate response is determined to be slowin relation to the activity level, then an adaptive rate pacing therapyis delivered to reduce the time of heart rate response to the activity.By using a combination of different sensors, heart rate specific todifferent activity levels can be measured to improve a patient'schronotropic response at different levels of activity, reducing thechance of over-pacing the heart failure patient.

Monitoring intrinsic heart rates and classifying activity levels by trueactivity events (e.g., sustained activity events), as well as measuringheart rate kinetics to the onset of activities, can be combined withprofiling of the patient's heart rate to specific workloads to allow forcustom tailoring of paced rates as compared to the current standard ofadaptive rate pacing. For example, therapies for increasing heart ratekinetics to the onset of activity in heart failure patients may beprogrammable with respect to the rate of increased pacing rate for theactivity. In addition, the patient's own intrinsic heart rate ispreferably used as a target for the appropriate heart rate for theactivity. The device may also be programmed as to specified paced heartrates that are not to be exceeded for specific activities.

Turning now to FIG. 1, there is illustrated a method 100 for reducing apatient's mean heart rate response to the onset of activity inaccordance with embodiments of the present invention. According to themethod 100 shown in FIG. 1, the onset of patient activity, such asexercise, is determined 102. A determination is made 104 as to whetheror not the patient activity is sustained. For example, the determination104 typically involves determining that the activity has been sustainedfor a period of time that is reflective of a steady-state activity.

If it is determined that the patient activity is sustained, adetermination is made 106 as to whether or not the patient's heart rateresponse to the sustained activity is slow. For example, the patient'sintrinsic heart rate response may be measured and evaluated as to thekinetic response of the patient's heart rate to the activity. If thepatient's heart rate response to the activity is determined to be slow,a pacing therapy is delivered 108 to the patient at a rate greater thanthe patient's intrinsic heart rate. The pacing therapy is typically anadaptive rate pacing therapy.

This pacing therapy is preferably adjusted based on a heart rateresponse profile developed for the patient. For example, the pacingtherapy may utilize the patient's own intrinsic heart rate-to-minuteventilation slope as a baseline measure to apply adaptive rate pacingduring the exercise onset period.

Once the patient reaches steady-state activity, the patient's ownintrinsic rate for the given workload is used to make adjustments to thepacing therapy, such as by governing upper rate pacing in order toreduce the chance of over-pacing the patient. In addition, the AV delayof the pacing therapy may be adjusted when adaptively adjusting thepacing rate during the exercise onset period (i.e., the kinetic phase).In general, the AV delay is typically extended out, within a range of0-120 ms.

The minute ventilation response to the steady state exercise can bemonitored to allow for a change in the sensed AV delay was well as inthe paced AV delay. For a given level of work, the AV delay can beautomatically adapted to result in a lower minute ventilation responseto the level of work. Automatically adjusting or optimizing the AV delayand/or VV delay parameters in the context of the present invention maybe implemented in a manner disclosed in commonly owned, co-pending U.S.Patent Publications 2005/0137632 and 2002/0120311, and in U.S. Pat. No.6,351,673, all of which are hereby incorporated herein by reference.

In FIG. 2, there is illustrated a method 200 of reducing a patient'smean heart rate response to the onset of activity in accordance withembodiments of the present invention. According to the method 200 shownin FIG. 2, a patient's intrinsic heart rate response to a patientactivity is measured 202, such as by use of an implantable minuteventilation sensor or pressure sensor of a known configuration. Thepatient's activity is measured, such as by use of an implantableaccelerometer of a known configuration. An output signal produced by theaccelerometer is evaluated to determine 204 whether or not the patientis engaged in a sustained activity. Patient activity and sustaining ofsame as measured by the accelerometer may be confirmed using the minuteventilation sensor or pressure sensor. A valid activity event may bedetermined when the respective output signals of the accelerometer andminute ventilation or pressure sensors are in agreement that the patientis indeed engaged in a sustained activity.

If the patient in engaged in a sustained activity, a determination ismade 206 as to whether or not the patient's intrinsic heart rate is slowduring the kinetic phase of the onset to the sustained activity. If thepatient's intrinsic heart rate during the kinetic phase of the onset tothe sustained activity determined to be slow, a pacing therapy isdelivered 208 above the patient's intrinsic heart rate in a manner thatreduces the patient's heart rate response time to steady-state. Ingeneral, the pacing therapy is delivered at a rate sufficient to improvea chronotropic response of the patient to the sustained activity,without overpacing the patient.

If the patient's intrinsic heart rate during the kinetic phase of theonset to the sustained activity not determined to be slow, a pacingtherapy is withheld 210. In this regard, energy associated with adaptiverate pacing therapy that may otherwise be expended in accordance with aconventional adaptive rate pacing approach is conserved.

FIG. 3 is a graph showing various aspects of an adaptive rate pacingtherapy that improves a patient's mean heart rate response to the onsetof activity implemented in accordance with the principles of the presentinvention. FIG. 3 shows an accelerometer output signal 306 superimposedon a curve 302 representative of a heart failure patient's intrinsicheart rate 302 at varying workloads. According to embodiments of thepresent invention, the accelerometer output signal 306 is monitored todetermined when a patient becomes active and when patient activity isconsidered sustained.

For example, a threshold may be established for the accelerometer outputsignal 306 that discriminates patient activeness that is of interest,such as from exercise, from sleep and wake-rest activities. For example,an accelerometer output signal 306 of less than 15 milli-g may beconsidered non-activity for purposes of the adaptive rate pacing therapyof the present invention. Accelerometer output signals above 20-25milli-g are generally indicative of patient activity levels of interest.

A sustained patient activity may be determined based on a minimum periodof time during which the patient has been engaged in an activity ofinterest. For example, a sustained patient activity may be determined ifthe patient has been engaged in an activity for at least 30 seconds,where that activity is associated with an accelerometer output signalthat exceeds a predetermined activity threshold (e.g., >30 mill-g for aminimum of 30 seconds).

Depending on various factors, such as the patient's age, health, andheart failure status, the minimum period of time for declaring that thepatient is engaged in a sustained activity may range from about 30seconds to about 6 minutes. The accelerometer output signal 306 may beaveraged or smoothed in order to filter out spurious short periods ofbelow-threshold activity during an otherwise acceptable above-thresholdactivity. Other techniques may be used to determine if a sustained levelof activity has been achieved by the patient. For example, the patient'sstroke volume may be measured, and a determination may be made as towhether or not the patient's stroke volume has reached a steady-statevalue in response to the patient activity (which may take at least about30-40 seconds or more).

As shown in FIG. 3, accelerometer output signal 306 is below apredetermined activity threshold until time t_(OA), which represents theonset of patient activity. The amplitude of accelerometer output signal306 increases significantly at time t_(OA), and thereafter increasesmore slowly, indicating patient engagement in the activity at asustained intensity. In this illustrative example, time t_(OA) indicatesthe onset of a qualifying sustained patient activity.

In response to determining that the patient is engaged in a sustainedactivity at time t_(OA), the patient's intrinsic heart rate signal 302is evaluated to determine if the patient's heart rate response to theonset of activity is slow. In FIG. 3, the time t_(SS-1) represents thetime at which the patient's intrinsic heart rate during the kineticphase has reached steady-state. The time period t_(RSS-1) represents theduration of time for the patient's intrinsic heart rate during thekinetic phase to reach steady-state as measured from the time t_(OA)(onset of sustained patient activity).

In FIG. 3, it is determined that the patient's intrinsic heart rateresponse 302 to the onset of patient activity is slow. Thisdetermination may be based on the patient's own intrinsic heartrate-to-minute ventilation slope derived from intrinsic heart rate curve302. One particular approach to making this determination, as will bediscussed with reference to FIGS. 4 and 5, involves the development anduse of a heart rate response-to-workload profile developed for thepatient and accessed during delivery of adaptive rate pacing therapy.

In response to determining that the patient's intrinsic heart rateresponse 302 to the onset of patient activity is slow, a pacing therapyis delivered to the patient. The pacing therapy increases the patient'sheart rate above intrinsic as is shown by paced heart rate signal 304.As can be seen in FIG. 3, the pacing rate is adaptively adjusted toreduce the time of the patient's heart rate response to the onset ofactivity. This time for the patient's heart rate response to reachsteady-state during the activity period in response to the adaptive ratepacing therapy is denote as time t_(SS-2). The time period t_(RSS-2)represents the duration of time for the patient's paced heart rateduring the kinetic phase to reach steady-state relative to the timet_(OA). In the illustrative example shown in FIG. 3, the time of thepatient's heart rate response to the onset of activity has been reducedby time duration t_(ΔSS) due to delivery of the adaptive rate pacingtherapy.

Referring now to FIG. 4, there is illustrated a method 400 fordeveloping a patient profile useful for implementing an adaptive ratepacing therapy for reducing a patient's mean heart rate response to theonset of activity in accordance with embodiments of the presentinvention. According to the method 400 shown in FIG. 4, a learning phaseor procedure for developing the patient profile is initiated 402. Thelearning phase shown in FIG. 4 is preferably performed followingimplantation of the patient-implantable medical device. The learningphase may be repeated over time as needed. For example, the learningphase shown in FIG. 4 may be invoked in accordance with a schedule or ondemand by a clinician. The learning phase may also be repeated when achange in a patient's heart failure status is detected, whether suchchange is indicative of an improved or worsened status.

The learning phase involves acquiring various physiological andnon-physiologic data about the patient. For example, during the learningphase, heart rate (HR) and minute ventilation (MV or VE) data may beacquired 404 for the patient a varying activity levels. In addition,data on the patient's mean heart rate response time (MRT) may beacquired or computed 406 for varying activity levels. These data arepreferably acquired during normal day-to-day activities of the patient.As such, the patient need not be subject to special exercises or testingin order to develop the patient profile data, although such may beconducted if desired.

These physiological data and corresponding activity level data arestored 408 in a suitable data structure, such as a look-up table orother array structure. These data may also be stored in the form ofmathematical functions derived from curve fitting the data. The data maybe organized using a variety of techniques. For example, the data may beacquired and subject to binning, by which HR, VE, and MRT values areassociated with ranges of activity levels, expressed in milli-g unitsfor example. An example of this technique is shown in FIG. 5.

According to other approaches, HR, VE, MRT, and activity level valuesmay be grouped using techniques that look for commonality among featureswithin data of interest. For example, clustering may be performed usingtechniques such as a K-Means clustering algorithm, self-organizing mapalgorithms, or other data clustering algorithms. It is understood thatuseful patient profile data need not include all of HR, VE, and MRTparameters, but may include one or two of these parameters (e.g., HR andVE in combination or MRT solely). Moreover, physiological andnon-physiological data other than HR, VE, and MRT data may be includedin the patient's profile data.

The learning phase may continue until a sufficient amount of data isacquired for a sufficiently wide distribution of patient activitylevels, at which time the learning phase may be terminated 410. Thelearning phase may alternatively be a continuous (or repeatedly invoked)subroutine that continuously updates the patient profile data.

Having established the patient's heart rate response-to-workloadprofile, this profile data may be accessed 412 during adaptive ratepacing therapy for reducing a patient's mean heart rate response to theonset of activity in accordance with embodiments of the presentinvention.

FIG. 5 is a block diagram of a device 502 configured to deliver adaptiverate pacing therapy in accordance with embodiments of the presentinvention. Device 502 may alternatively be configured as a monitor-onlydevice, in which patient profile data and other data (e.g., cardiacactivity and/or respiration data) may be acquired.

Device 502 includes a processor 504 coupled to memory 506. Processor 504is coupled to a number of sensors, including an accelerometer 512 and aphysiological sensor, such as a minute ventilation sensor 514. Theaccelerometer 512 and minute ventilation sensor 514 may be implementedin a known manner. Processor 504 is also coupled to a number ofelectrodes 516 configured to sense electrical activity of the heart. Theelectrodes 516 may include one or more (or combinations) of transvenous,endocardial, and epicardial electrodes (i.e., intrathoracic electrodes),and/or subcutaneous, non-intrathoracic electrodes, including can,header, and indifferent electrodes, and subcutaneous array or leadelectrodes (i.e., non-intrathoracic electrodes).

Processor 504 is coupled to detection circuitry 520 and energy deliverycircuitry 522. Detection circuitry 520 and energy delivery circuitry 522are respectively coupled to electrodes 516. Detection circuitry 520 isconfigured to detect cardiac activity and events using known techniques.Energy delivery circuitry 522 is configured to deliver pacing therapiesusing known techniques. Energy delivery circuitry 522 is also configuredto deliver adaptive rate pacing therapies for reducing a patient's meanheart rate response to the onset of activity in accordance withembodiments of the present invention. Energy delivery circuitry 522 mayalso be configured to deliver high energy cardioversion anddefibrillation energy when implemented as an implantablecardioverter/defibrillator (ICD). Energy delivery circuitry 522 may beomitted in devices implemented as monitor-only devices.

Memory 506 may be configured to include or support patent profile data508. For example, and as shown in FIG. 5, memory 506 may be configuredto support a look-up table 510 of binned patent profile data. In thisillustrative example, values for MRT, HR, and VE are binned according totheir associated activity level values, expressed in terms of milli-g.As shown, a set of MRT, HR, and VE values are associated with activitylevel ranges of 10 milli-g in width, up to the accelerometer's uppermaximum sensitivity limit (typically around 200-250 milli-g). It isunderstood that the width of the activity level ranges need not beequal, but may vary. The parameters associated with binning may beestablished automatically (e.g., by the implantable medical device) orby the physician (or a combination of both means).

For example, a given activity level range that has MRT, HR, and VEvalues that vary widely may be divided into two or more sub-ranges. Thisdivision processes may be based on the standard deviation of MRT, HR,and VE values exceeding a preestablished threshold, for example. Varyingthe width of the activity level ranges may provide for enhanced adaptiverate pacing control, such as by providing for more gradual changesbetween pacing rate adjustments.

As was discussed previously, an adaptive rate pacing methodology of thepresent invention may be implemented in a wide variety of implantablemedical devices, such as cardiac sensing and/or stimulation devices. Forexample, various embodiments described herein may be used in connectionwith devices that provide for heart failure monitoring, diagnosis,and/or therapy. A patient implantable medical device or PIMD of thepresent invention may incorporate HF features involving dual-chamber orbi-ventricular pacing/therapy, cardiac resynchronization therapy,cardiac function optimization, or other HF related methodologies. Forexample, a PIMD of the present invention may incorporate features of oneor more of the following references: commonly owned U.S. patentapplication Ser. No. 10/270,035, filed Oct. 11, 2002, entitled “TimingCycles for Synchronized Multisite Cardiac Pacing;” and U.S. Pat. Nos.6,411,848; 6,285,907; 4,928,688; 6,459,929; 5,334,222; 6,026,320;6,371,922; 6,597,951; 6,424,865; and 6,542,775, each of which is herebyincorporated herein by reference.

Certain configurations illustrated herein are generally described ascapable of implementing various functions traditionally performed by animplantable cardioverter/defibrillator (ICD), and may operate innumerous cardioversion/defibrillation modes as are known in the art.Examples of ICD circuitry, structures and functionality, aspects ofwhich may be incorporated in a PIMD of the present invention, aredisclosed in commonly owned U.S. Pat. Nos. 5,133,353; 5,179,945;5,314,459; 5,318,597; 5,620,466; and 5,662,688, which are herebyincorporated herein by reference.

In particular configurations, systems and methods may perform functionstraditionally performed by pacemakers, such as providing various pacingtherapies as are known in the art, in addition tocardioversion/defibrillation therapies. Examples of pacemaker circuitry,structures and functionality, aspects of which may be incorporated in aPIMD of the present invention, are disclosed in commonly owned U.S. Pat.Nos. 4,562,841; 5,284,136; 5,376,106; 5,036,849; 5,540,727; 5,836,987;6,044,298; and 6,055,454, which are hereby incorporated herein byreference.

A PIMD in accordance with the present invention may implement diagnosticand/or monitoring functions to the exclusion of cardiac stimulationtherapy (i.e., monitor-only embodiments). Examples of cardiac monitoringcircuitry, structures and functionality, aspects of which may beincorporated in a PIMD of the present invention, are disclosed incommonly owned U.S. Pat. Nos. 5,313,953; 5,388,578; and 5,411,031, whichare hereby incorporated herein by reference.

Referring again to FIG. 5, processor 504 is coupled to communicationscircuitry 518. Communications circuitry 518 may be configured to effectcommunications between the device of FIG. 5 and one or more externaldevices 528. External device 528 may be representative of a programmer,a networked patient management system, a portable or hand-heldcommunicator, or other patient-external system. The external device 528is typically coupled to a user interface, such as a graphical userinterface or other interface that provides a display. The user interfacepreferably includes a user actuatable input/output device, such as akeyboard, touch screen sensor, mouse, light pen, and the like. The userinterface may be used by the clinician to make adjustments to parametersof the PIMD, including modifications to the patient's profile data 508,for example.

As was discussed above, A PIMD of the present invention may beimplemented to communicate with a patient management server or networkvia an appropriate communications interface or an external programmer. APIMD of the present invention may be used within the structure of anadvanced patient management (APM) system. The advanced patientmanagement system allows physicians to remotely and automaticallymonitor cardiac and respiratory functions, as well as other patientconditions. In one example, a PIMD implemented as a cardiac pacemaker,defibrillator, or resynchronization device may be equipped with varioustelecommunications and information technologies that enable real-timedata collection, diagnosis, and treatment of the patient. Various PIMDembodiments described herein may be used in connection with advancedpatient management. Methods, structures, and/or techniques describedherein, which may be adapted to provide for remote patient/devicemonitoring, diagnosis, therapy, or other APM related methodologies, mayincorporate features of one or more of the following references: U.S.Pat. Nos. 6,221,011; 6,270,457; 6,277,072; 6,280,380; 6,312,378;6,336,903; 6,358,203; 6,368,284; 6,398,728; and 6,440,066, which arehereby incorporated herein by reference.

Referring now to FIG. 6, there is illustrated an embodiment of a PIMDconfigured to implement methodologies of the present invention.According to one implementation, a PIMD may be configured formonitor-only operation. According to another implementation, a PIMD maybe configured to deliver one or both of pacing therapies andcardioversion/defibrillation therapies. Although the followingdiscussion describes various energy delivery aspects, it is understoodthat these aspects may be excluded in a monitor-only implementation of aPIMD according to the present invention.

In the illustrative implementation shown in FIG. 6, a PIMD includes acardiac rhythm management device (CRM) 700 including an implantablepulse generator 705 electrically and physically coupled to anintracardiac lead system 710. Portions of the intracardiac lead system710 are shown inserted into the patient's heart 790. The intracardiaclead system 710 includes one or more electrodes and/or sensorsconfigured to sense electrical cardiac activity of the heart, deliverelectrical stimulation to the heart, and sense the patient'stransthoracic impedance or transthoracic total impedance. Other sensorsmay be provided on intracardiac lead system 710, including sensors thatmeasure blood (internal filling) pressure, blood flow, and/or bloodtemperature, acceleration and/or body acoustics, and/or otherphysiological parameters. Portions of the housing 701 of the pulsegenerator 705 may optionally serve as a can electrode.

Communications circuitry is disposed within the housing 701 forfacilitating communication between the pulse generator 705 and anexternal communication device, such as a portable or bed-sidecommunication station, patient-carried/worn communication station (e.g.,communicator), external programmer or advanced patient management systeminterface, for example. The communications circuitry may also facilitateunidirectional or bidirectional communication with one or moreimplanted, external, cutaneous, or subcutaneous physiologic ornon-physiologic sensors, patient-input devices and/or informationsystems.

The pulse generator 705 incorporates an activity detector 720 that maybe used to sense patient activity, as well as various respiration andcardiac related conditions. For example, the activity detector 720 maybe optionally configured to sense snoring, activity level, and/or chestwall movements associated with respiratory effort, for example. Theactivity detector 720 is preferably implemented as an accelerometer orother rate sensor positioned in or on the housing 701 of the pulsegenerator 705. For an activity detector 720 implemented as anaccelerometer, the activity detector 720 may also provide respiratory,e.g. rales, coughing, and cardiac, e.g. S1-S4 heart sounds, murmurs, andother acoustic information. An accelerometer may be used to developrespiration waveforms from which various respiratory parameters may bedeveloped.

The lead system 710 and pulse generator 705 of the CRM 700 mayincorporate one or more transthoracic impedance sensors that may be usedto acquire the patient's respiration waveform, or otherrespiration-related information. The transthoracic impedance sensor mayinclude, for example, one or more intracardiac electrodes 741, 742,751-755, 763 positioned in one or more chambers of the heart 790. Theintracardiac electrodes 741, 742, 751-755, 763 may be coupled toimpedance drive/sense circuitry 730 positioned within the housing of thepulse generator 705.

In one implementation, impedance drive/sense circuitry 730 generates acurrent that flows through the tissue between an impedance driveelectrode 751 and a can electrode on the housing 701 of the pulsegenerator 705. The voltage at an impedance sense electrode 752 relativeto the can electrode changes as the patient's transthoracic impedancechanges. The voltage signal developed between the impedance senseelectrode 752 and the can electrode is detected by the impedance sensecircuitry 730. Other locations and/or combinations of impedance senseand drive electrodes are also possible. The CRM 700 may compute thepatient's minute ventilation using known techniques based on thepatient's transthoracic impedance changes.

The lead system 710 may include one or more cardiac pace/senseelectrodes 751-755 positioned in, on, or about one or more heartchambers for sensing electrical signals from the patient's heart 790and/or delivering pacing pulses to the heart 790. The intracardiacsense/pace electrodes 751-755, such as those illustrated in FIG. 6, maybe used to sense and/or pace one or more chambers of the heart,including the left ventricle, the right ventricle, the left atriumand/or the right atrium. The lead system 710 may include one or moredefibrillation electrodes 741, 742 for deliveringdefibrillation/cardioversion shocks to the heart.

The lead system 710 may include one or more leads each having one ormore electrodes that extend into the heart. FIG. 6 shows three suchleads, one that extends into the right atrium, one that extends into theright ventricle, and one that extends into a coronary vein for placementat the surface of the left ventricle. The left ventricular lead, inparticular, includes an LV distal electrode 755 and an LV proximalelectrode 754 located at appropriate locations in or about the leftventricle for pacing and/or sensing the left ventricle. The leftventricular lead may be guided into the right atrium of the heart viathe superior vena cava. From the right atrium, the left ventricular leadmay be deployed into the coronary sinus ostium, the opening of thecoronary sinus. The lead may be guided through the coronary sinus to acoronary vein of the left ventricle. This vein is used as an accesspathway for leads to reach the surfaces of the left ventricle that arenot directly accessible from the right side of the heart.

The pulse generator 705 may include circuitry for detecting cardiacarrhythmias and/or for controlling pacing or defibrillation therapy inthe form of electrical stimulation pulses or shocks delivered to theheart through the lead system 710. The pulse generator 705 may alsoincorporate circuitry, structures and functionality of the implantablemedical devices disclosed in commonly owned U.S. Pat. Nos. 5,203,348;5,230,337; 5,360,442; 5,366,496; 5,397,342; 5,391,200; 5,545,202;5,603,732; and 5,916,243; 6,360,127; 6,597,951; and U.S. PatentPublication No. 2002/0143264, which are hereby incorporated herein byreference.

For purposes of illustration, and not of limitation, various embodimentsof devices implemented in accordance with the present invention providefor monitor-only operation. FIG. 7 shows an embodiment of a monitor-onlyPIMD configuration. Such a PIMD may be implanted under the skin in thechest region of a patient. A PIMD may, for example, be implantedsubcutaneously such that all or selected elements of the device arepositioned on the patient's front, back, side, or other body locationssuitable for sensing cardiac activity. It is understood that elements ofthe PIMD may be located at several different body locations, such as inthe chest, abdominal, or subclavian region with electrode elementsrespectively positioned at different regions near, around, in, or on theheart.

The primary housing (e.g., the active or non-active can) of the PIMD,for example, may be configured for positioning outside of the rib cageat an intercostal or subcostal location, within the abdomen, or in theupper chest region (e.g., subclavian location, such as above the thirdrib). In general, one or more electrodes may be located on the primaryhousing and/or at other locations about, but not in direct contact withthe heart, great vessel or coronary vasculature (such embodimentsreferred to herein as subcutaneous, non-intrathoracic embodiments).

In a further implementation, for example, one or more electrodesubsystems or electrode arrays may be used to sense cardiac activity ina PIMD configuration employing an active can or a configurationemploying a non-active can. Electrodes may be situated at anteriorand/or posterior locations relative to the heart. Examples of usefulelectrode locations and features that may be incorporated in variousembodiments of the present invention are described in commonly owned,co-pending U.S. patent application Ser. Nos. 10/465,520 filed Jun. 19,2003, entitled “Methods and Systems Involving Subcutaneous ElectrodePositioning Relative to a Heart,” and 10/738,608 filed Dec. 17, 2003,entitled “Noise Canceling Cardiac Electrodes,” which are herebyincorporated herein by reference.

In one configuration, as is illustrated in FIG. 7, electrode subsystemsof a PIMD system are arranged outside the rib cage in relation to apatient's heart 810. The PIMD system includes a first electrodesubsystem, comprising a can electrode 802, and a second electrodesubsystem 804 that may include at least two electrodes or at least onemulti-element electrode for sensing cardiac electrical activity.

The can electrode 802 is positioned on the housing 801 that encloses thePIMD electronics. In one embodiment, the can electrode 802 includes theentirety of the external surface of housing 801. In other embodiments,various portions of the housing 801 may be electrically isolated fromthe can electrode 802 or from tissue.

The components, functionality, and structural configurations depictedherein are intended to provide an understanding of various features andcombination of features that may be incorporated in a PIMD orpatient-external medical device. It is understood that a wide variety ofPIMDs, external medical devices, and other implantable cardiacmonitoring and/or stimulation device configurations are contemplated,ranging from relatively sophisticated to relatively simple designs. Assuch, particular medical device configurations may include particularfeatures as described herein, while other such device configurations mayexclude particular features described herein.

Various modifications and additions can be made to the embodimentsdiscussed hereinabove without departing from the scope of the presentinvention. Accordingly, the scope of the present invention should not belimited by the particular embodiments described above, but should bedefined only by the claims set forth below and equivalents thereof.

1. An implantable device, comprising: electrodes for electricallycoupling to a patient's heart; an activity sensor configured to detectactivity of the patient; a physiologic sensor configured to measurephysiologic demand of the patient; memory configured to store patientprofile data, the patient profile data comprising heart rate responsedata relative to varying workloads established for the patient; and aprocessor coupled to the electrodes, activity sensor, physiologicsensor, and memory, the processor configured to determine onset ofsustained patient activity and that a heart rate parameter of thepatient has reached a steady-state in response to the sustained patientactivity, the processor configured to determine a timing relationshipbetween the onset of sustained patient activity and the heart rateparameter reaching the steady-state, and to one or both of initiate andchange a pacing therapy based on a comparison of the timing relationshipto a stored patient profile of the patient's heart rate response tovarying workloads indicating slow heart rate response to the sustainedpatient activity.
 2. The device of claim 1, wherein the processor isconfigured to withhold the pacing therapy in response to the processordetermining that the patient's heart rate response to the sustainedactivity is not slow.
 3. The device of claim 1, wherein the processor isconfigured to determine sustaining of the patient activity in responseto sensing an output signal produced by the activity sensor indicativeof sustained patient activity for a time duration exceeding a thresholdranging between about 30 seconds and about 6 minutes.
 4. The device ofclaim 1, wherein the processor is configured to determine sustaining ofthe patient activity in response the patient's stroke volume reaching asteady-state value in response to the activity.
 5. The device of claim1, wherein the processor is configured to determine sustaining of thepatient activity in response to sensing an output signal produced by theactivity sensor and the physiologic sensor, respectively.
 6. The deviceof claim 1, wherein the activity sensor comprises an accelerometer andthe physiologic sensor comprises a minute ventilation sensor or apressure sensor.
 7. The device of claim 1, wherein the processor isconfigured to adjust an upper rate limit of the pacing therapy based onthe patient's profile.
 8. The device of claim 1, wherein the processoris configured to adjust one or both of an AV delay parameter and a VVdelay parameter of the pacing therapy.
 9. The device of claim 1, whereinthe processor is configured to acquire patient profile data comprisingone or both of the patient's intrinsic heart rate and minuteventilation, and to store the patient profile data in the memory. 10.The device of claim 1, wherein the processor is configured to acquirepatient profile data comprising mean heart rate response time data atvarying activity levels, and to store the patient profile data in thememory.
 11. The device of claim 1, wherein the processor determinesslowness of the patient's heart rate response based on patient profiledata associated with an activity level of the profile corresponding tothe patient's actual activity level.
 12. An implantable device,comprising: electrodes for electrically coupling to a patient's heart;an activity sensor configured to detect activity of the patient; aphysiologic sensor configured to measure physiologic demand of thepatient; memory configured to store patient profile data, the patientprofile data comprising heart rate response data relative to varyingworkloads established for the patient; and a processor coupled to theelectrodes, activity sensor, physiologic sensor, and memory, theprocessor configured to determine onset of sustained patient activityand whether the patient's intrinsic heart rate response is slow during akinetic phase of the onset of the sustained activity, the processorconfigured to initiate or change a pacing therapy to deliver pacingpulses at a rate above the patient's intrinsic heart rate based at leastin part on the patient profile data if the patient's intrinsic heartrate response during the kinetic phase is determined by the processor tobe slow.
 13. The device of claim 12, wherein the processor is configuredto initiate or change the pacing therapy to deliver pacing pulses at arate sufficient to improve a chronotropic response of the patient to thesustained activity.
 14. The device of claim 12, wherein the processor isconfigured to initiate or change the pacing therapy to deliver pacingpulses at a rate sufficient to improve a chronotropic response of thepatient to the sustained activity without overpacing the patient. 15.The device of claim 12, wherein the processor is configured to initiateor change the pacing therapy to deliver pacing pulses at a rate thatimproves a patient's chronotropic response of the patient at differentlevels of patient activity.
 16. The device of claim 12, wherein theprocessor is configured to initiate or change the pacing therapy todeliver pacing pulses at a rate sufficient to increase the patient'sheart rate response for reaching a steady-state exercise level of thesustained activity.
 17. The device of claim 12, wherein the processor isconfigured to determine onset of sustained patient activity by sensingthat the patient has been active for a time duration exceeding athreshold ranging between about 30 seconds and about 6 minutes.
 18. Thedevice of claim 12, wherein the processor is configured to determineonset of sustained patient activity by sensing that the patient's strokevolume has reached a steady-state value in response to the patientactivity.
 19. The device of claim 12, wherein the processor isconfigured adjust one or both of an AV delay parameter and a VVparameter of the pacing therapy to deliver pacing pulses at the rateabove the patient's intrinsic heart rate.
 20. An implantable device,comprising: means for determining onset of sustained patient activity;means for determining that a heart rate parameter of the patient hasreached a steady-state in response to the sustained patient activity;means for determining a timing relationship between the onset ofsustained patient activity and the heart rate parameter reaching thesteady-state; and means for one or both of initiating and changing apacing therapy based on a comparison of the timing relationship to aprofile of the patient's heart rate response to varying workloadsindicating slow heart rate response to the sustained patient activity.